A Safety Study of RTA 744 in Recurrent, Progressive or Refractory Neoplastic Meningitis

NCT00527410 | Terminated Phase 1

• 1 other identifier: RTA 744-C-0601
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This study assesses the tolerability, safety, efficacy and pharmacokinetics of RTA 744 in recurrent neoplastic meningitis.

Conditions

Leptomeningeal Carcinomatosis

Outcome Measures

Primary Outcomes (2)

• Determine the tolerability of RTA 744 Injection in patients with leptomeningeal disease (LMD) secondary to any type of primary tumor.

  evaluation at end of cycle 1 for each cohort

• Characterize the multiple-dose pharmacokinetics of RTA 744 in plasma and CSF in a selected group of 6-10 patients who will receive RTA 744 at or near the maximum tolerated dose (MTD).

  end of study

Secondary Outcomes (2)

• Document any potential antitumor activity.

  after every even numbered treatment cycle

• Correlate pharmacokinetic information with clinical (efficacy and safety) responses.

  end of study

Study Arms (1)

RTA 744

EXPERIMENTAL

RTA 744 injection administered intravenously for a maximum of 18 cycles (54 weeks). Dose escalation based on four dose levels and occurance of dose limiting toxicity (DLT).

Drug: RTA 744

Interventions

RTA 744 DRUG

Aqueous solution of RTA 744 is packaged in 5 ml vials - 1 mg/ ml. The drug is mixed in D10W and infused over 2 hours on three consecutive days.

RTA 744

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic confirmation of primary malignancy. All primary tumor types may be enrolled.
• Neoplastic meningitis/leptomeningeal metastasis refractory to conventional therapy with presence of tumor cells on cytology, OR neuroimaging evidence of leptomeningeal tumor by MRI.
• Not eligible for higher priority clinical trial.
• Have recovered from side effects of any surgical resection.
• A stable dose of steroid for at least 7 days prior to the Gd-MRI.
• Karnofsky Performance Status (KPS) of ≥ 60.
• Laboratory Parameters: ANC ≥ 1.5 x 109/L; Hgb ≥ 9 g/dl; Platelets ≥ 100 x 109/L; AST and ALT ≤ 3.0 x ULN; Serum bilirubin ≤ 1.5 x ULN; Serum creatinine ≤ 1.5 x ULN; 24 hour creatinine clearance ≥ 50 ml/min
• Life expectancy of at least 8 weeks.
• Written informed consent obtained.

You may not qualify if:

• Concurrent therapy for leptomeningeal disease or other malignancy.
• Clinical evidence of obstructive hydrocephalus or compartmentalization of CSF flow.
• Cumulative doses: doxorubicin \> 450 - 550 mg/m2, epirubicin \> 800-1000 mg/m2, idarubicin \>130-150 mg/m2 and daunorubicin \> 400-550 mg/m2.
• Anticonvulsant medications or other types of medications which are known to induce the CYP450 enzymes.
• Pregnancy or breast feeding, or adults (male or female) of reproductive potential not employing an effective method of birth control
• Total 24 hour urinary protein \> 500 mg.
• Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study
• Impaired cardiac function, other significant prior cardiac disease or arrhythmia of any type
• Myocardial infarction ≤ 6 months prior
• History of CHF or arrhythmias
• Therapeutic doses of anticoagulant therapy (prophylactic dosing is allowed)
• Investigational drugs less than 4 weeks prior; intrathecal chemotherapy within 2 weeks prior; systemic cytotoxic chemotherapy within 4 weeks prior (6 weeks for nitrosourea or mitomycin-C or 2 weeks for vincristine); radiation therapy within 2 weeks prior; any medication known to cause QT interval prolongation
• Any surgery \<2 weeks prior

Sponsors & Collaborators

• Biogen: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Meningeal Carcinomatosis

Interventions

WP 744

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2007
• First Posted: September 10, 2007
• Study Start: October 31, 2006
• Primary Completion: December 1, 2008
• Last Updated: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)